VASST: Vasopressin Added to Norepinephrine in Septic Shock

Adding vasopressin didn't beat norepi alone overall, but helped in 'less-severe' shock subgroup.

Population

778 septic-shock adults requiring norepi ≥5 mcg/min.

Intervention

Low-dose vasopressin 0.01-0.03 U/min added to baseline norepi.

Comparison

Norepi alone (placebo infusion).

Outcome

28-day mortality; secondary: 90-day mortality, organ failure.

Double-blind RCT across 27 ICUs. Both arms received open-label norepi titrated to MAP ≥65. Pre-specified subgroup: 'less severe' shock = norepi requirement <15 mcg/min at randomization.

• 28-day mortality: 35.4% vasopressin vs 39.3% norepi alone (P=0.26) — null overall.
• Less-severe subgroup (<15 mcg/min norepi): 26.5% vs 35.7% (P=0.05) — vasopressin benefit.
• More-severe subgroup: no difference.
• Adverse events similar; no excess in mesenteric/digital ischemia.

Add vasopressin 0.03 U/min (fixed dose, NOT titrated) when norepi is at ~0.25 mcg/kg/min and MAP is below goal — Surviving Sepsis 2021 guideline. Vasopressin is catecholamine-sparing (lowers norepi requirement), restores vascular tone via V1 receptors, and avoids the tachyphylaxis seen with prolonged catecholamine infusions. Don't expect it to rescue refractory profound shock, but it has a clear role as a SECOND-LINE agent before climbing norepi past 0.5 mcg/kg/min.

• Pre-specified subgroup analyses are hypothesis-generating, not confirmatory.
• Did not address vasopressin as MONOTHERAPY (no one would have studied it that way).
• Heterogeneity in steroid co-administration may have affected results (later analyses suggested interaction).

1. When in your norepi escalation do you add vasopressin? What's your institutional practice?
2. Why fixed dose (0.03 U/min) rather than titrated like norepi?
3. Should vasopressin be first-line in vasoplegic post-bypass shock (a different population)?